Skin cancer is the most commonly occurring cancer, accounting for 40% of all new cancer diagnoses and for about 2% of all cancer deaths (1). It is a disease in which cancer (malignant) cells are found in the outer layers of the skin.
There are three main types of skin cancer:
a) Non-melanoma-common types such as basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).
b) Melanoma-rare type, found in the cells that color the skin (melanocytes).
c) Actinic keratosis, pre-malignant skin lesion, often progresses to squamous cell cancer.
The incidence of melanoma and non-melanoma skin cancer appears to be increasing (2, 3), although melanoma incidence rates may have stabilized in the 1990s (4). Epidemiological evidence suggests that aging population, exposure to ultraviolet (UV) radiation and the sensitivity of an individual's skin to UV radiation are risk factors for skin cancer, although the type of exposure (high-intensity intermittent versus chronic) and pattern of exposure (continuous versus intermittent) may differ among the three main types of skin cancer (2, 3, 5).
Cancer is a disease of inappropriate tissue accumulation. Chemotherapeutic agents share one characteristic: they are usually more effective in killing or damaging malignant cells than normal cells. However the fact that they do harm normal cells indicates their potential for toxicity. Animal tumor investigations and human clinical trials have shown that drug combinations produce higher rates of objective response and longer survival than single agents. Combination drug therapy is therefore, the basis for most chemotherapy employed at present (DeVita, V. T. et al., 1975, Cancer 35:98).
Cancer treatment requires inhibitions of a variety of factors including tumor cell proliferation, metastatic dissemination of cancer cells to other parts of the body, invasion, tumor-induced neovascularization, and enhancement of host immunological responses and cytotoxicity. Conventional cancer chemotherapeutic agents have often been selected on the basis of their cytotoxicity to tumor cells. However, some anticancer agents have adverse effects on the patients immune system. Thus, it would be greatly advantageous if a cancer therapy or treatment could be developed that would afford non-cytotoxic protection against factors that might lead to progression of tumors. By virtue of the present invention, it has been discovered that canola extracts can be utilized to inhibit the proliferation of cancer cells.
Canola is a cruciferous crop which is mainly utilized for its extracted oil. After the oil has been extracted a protein rich meal remains which is used as a ruminant in animal diets. Further extraction of the canola meal yields minor components from canola, including, glucosinolates, phenolic acid esters and phenolic acids. The total content of selected minor components in Canola extracts from prior art methods are listed below:
μM/g extractmg/g extractProgoitrin8.523.45Gluconapin5.892.294-hydroxybrassicin3.221.55Glucobrassicanapin0.900.36Glucoalyssin0.640.27Napoleiferin0.540.23Glucobrassicin0.400.19Glucoraphanin0.220.09Sinigrine0.190.07Gluconasturtin0.190.08Neoglucobrassicin0.060.034-methoxyglucobrassicintraces—
Glucosinolates present in the extract from prior art methods from flaked, cooked canola seeds are listed below:
mg/g extract% contentTotal glucosinolates8.610.9%(flaked, cooked Canolaseeds)Total phenolic acids134.0013.4%(flaked, cooked Canolaseeds)Total phenolic acids53.155.3%(Canola meal)Free phenolic acids246.6424.7%(Canola meal extract afterhydrolysis)*The remaining components of extracts are mostly sugars and small amounts and saponins
Content of phenolic acids in the extract from prior art methods from canola meal (mg/g extract) are listed below:
ProtocatechuicCaffeicp-coumaricFerulicSinapicFreeTrace0.030.020.021.03phenolicacidsPhenolicTrace0.070.080.5650.75acidsliberatedfrom solubleestersPhenolic—Trace0.060.010.52acidsliberatedfrom solubleglycosides
Content of free phenolic acids in the extract from canola meal after hydrolysis according to prior art methods (ng/g extract) are listed below:
ProtocatechuicCaffeicp-coumaricFerulicSinapicTrace0.110.813.64242.08
Content of phenolic acids in flaked, cooked canola seeds according to prior art methods (mg/g extract) are listed below:
p-ProtocatechuicCaffeiccoumaricFerulicSinapicFree phenolicTraceTraceTrace0.021.18acidsPhenolic acidsTrace0.010.070.52131.95liberated fromsoluble estersPhenolic acids—TraceTraceTrace0.25liberated fromsolubleglycosides
U.S. Patent Application 20020090405 describes the use of canola extracts useful in inhibiting cell proliferation in at least one form of cancer. The canola extracts described therein do not contain more than about 24% sinapic acid content.
In addition to their role in the treatment of cancer, canola extracts may also be useful in the treatment of hyperlipidemias. The hyperlipidemias include six types of inheritable hyperlipoproteinemias; these types frequently are referred to as lipoprotein phenotypes. The major plasma lipids, including cholesterol and the triglycerides do not circulate freely in solution in plasma, but are bound to proteins and transported as macromolecular complexes called lipoproteins. The major lipoprotein phenotypes are chylomicrons, very low-density (pre-β) lipoproteins (VLDL), low-density (β-) lipoproteins (LDL), and high-density (α-) lipoproteins (HDL). Chylomicrons, the largest lipoproteins, carry exogenous glyceride from the intestine via the thoracic duct to adipocytes and muscle cells. VLDL carry endogenous glyceride primarily from the liver to adipocytes and muscle cells. VLDL is the main source of plasma LDL. Classification of inherited hyperlipoproteinemias according to phenotype is important, since dietary management and drug therapy are largely dependent on this information. (The Merck Manual, 16th edition, Robert Berkow and Andrew J. Fletcher, Merck & Co., Inc., Rahway, N.J. 1992).
U.S. Patent Application 20020090404 describes the use of canola extracts useful in treating hyperlipidemia. The canola extracts described therein do not contain more than about 24% sinapic acid content.
There exists a need in the art for canola extracts which are more potent than canola extracts known in the art for treating cancer and/or hyperlipidemia